S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis

Autor(es):Mostrar menos -

Mazo, Daniel F. C. ^[1] ; de Oliveira, Marcelo G. ^[2] ; Pereira, Isabel V. A. ^[1] ; Cogliati, Bruno ^[3] ; Stefano, Jose T. ^[1] ; de Souza, Gabriela F. P. ^[2] ; Rabelo, Fabiola ^[1] ; Lima, Fabiana R. ^[4] ; Alves, Venancio A. Ferreira ^[4] ; Carrilho, Flair J. ^[1] ; de Oliveira, Claudia P. M. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Gastroenterol, Hepatol Branch LIM 07, Clin Div, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil

^[3] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Dept Pathol LIMI4, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DRUG DESIGN DEVELOPMENT AND THERAPY; v. 7, p. 553-563, 2013.
• Citações Web of Science: 14

Resumo

S-Nitroso-N-acetylcysteine (SNAC) is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH) induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases {[}MMP]-13, -9, and -2), transforming growth factor beta-1 {[}TGF beta-1], collagen-1 alpha, and tissue inhibitors of metalloproteinase {[}TIMP-1 and -2] and oxidative stress (heat-shock proteins {[}HSP]-60 and -90) were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGF beta-1, and collagen-1 alpha. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH. (AU)

• Processo FAPESP: 08/56157-7 - Aspectos fisiopatogênicos e terapêuticos da fibrogênese e carcinogênese hepática experimental na doença hepática gordurosa não alcoólica: avaliação do efeito de doadores de óxido nítrico in vitro
• Beneficiário: Claudia Pinto Marques Souza de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 11/50514-5 - O efeito das interleucinas-6,-10 e -27 na perda de peso por restricao calorica.
• Beneficiário: Gabriela Freitas Pereira de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 08/52454-7 - Efeito anti-fibrogênico do doador de óxido nítrico s-nitroso-n-acetilcisteina (SNAC) na Esteato-hepatite não alcoólica e Cirrose experimental
• Beneficiário: Daniel Ferraz de Campos Mazo
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto